The estimated glucose disposal rate (eGDR) is associated with the incidence of incident stroke (IS). However, its role in predicting IS within the Circadian Syndrome (CircS), a multisystem metabolic disorder, remains unclear. A prospective cohort study was conducted with 3,128 adults (≥ 45 years) diagnosed with CircS and without baseline stroke, utilizing data from the China Health and Retirement Longitudinal Study (CHARLS). The primary outcome was the incidence of IS during the follow-up period. Analyses were performed using Cox proportional hazards models, restricted cubic spline (RCS), subgroup analysis, and area under the curve (AUC) assessments. Followed for a median of 108 months (2012–2020), 409 first-onset strokes (13.07%) occurred. After fully adjusting, eGDR (HR = 0.85, 95% CI: 0.80–0.89, p < 0.001), eGDR/CircS scores (eGDR divided by CircS component count, HR = 0.53, 95% CI: 0.44–0.63, p < 0.001), and cumulative eGDR (HR = 0.93, 95% CI: 0.91–0.95, p < 0.001) were associated with IS. Graded inverse associations were observed across quartile/tertile, with the highest eGDR quartile halving the risk compared to Q1 (HR = 0.42, 95% CI: 0.30–0.59, p < 0.001). Optimal eGDR level control (cluster class) conferred a lower risk than the poorest control (HR = 0.38, 95% CI: 0.28–0.53, p < 0.001). Dose–response relationships were significantly linear (p for overall < 0.001) for eGDR, eGDR/CircS scores, and cumulative eGDR with the risk of IS. Subgroup analyses confirmed that the protective association was stronger in younger (eGDR: p for interaction = 0.015) and men (eGDR: p for interaction = 0.020; eGDR/CircS scores: p for interaction = 0.015). AUCs were modest and similar for eGDR and eGDR/CircS (0.613 vs. 0.617). These findings support the use of eGDR-based metrics and longitudinal eGDR control as independent and potentially valuable tools for stroke risk stratification in patients with CircS.

Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders which results in accumulation of glycosaminoglycans throughout the body. MPS I is a subtype characterized by mutations in the α-L-iduronidase (IDUA) gene with subsequent multiorgan dysfunction. Here, we describe an adult patient with MPS I who presented with anasarca, as well as severely increased albuminuria, and was initially diagnosed with hyperthyroidism. Subsequent testing revealed clinical characteristics and deficient IDUA enzyme activity consistent with MPS I. Genetic testing identified two variants of interest in the IDUA gene: IDUA c·265C > T (p.R89W) and IDUA c.1403-2A > G. IDUA enzymatic activity was measured in HEK293T cells transfected with wildtype or p. R89W mutant IDUA expression constructs using the fluorogenic substrate 4-methylumbelliferyl-α-L-iduronide (4MU-iduronide). A minigene splicing assay was performed using IDUA exon 9–11 (including intron 9 and 10) DNA fragments cloned into the pMini-CopGFP vector, with the mutant plasmid containing the IDUA c.1403-2A > G variant generated using site-directed mutagenesis. HEK293T cells were transfected with either the wildtype or mutant plasmids, and splice products were separated by gel electrophoresis with distinct bands excised for Sanger sequencing. The IDUA c·265C > T (p.R89W) mutant construct was cloned into HEK293T cells and showed significantly decreased intracellular (10.86 ± 0.36

Disruption of circadian rhythms is increasingly recognized as a contributor to cognitive dysfunction, but its role in gestation-associated cognitive changes remains unexplored. Here we combine human cognitive screening with a comprehensive longitudinal mouse model to investigate whether gestational cognitive impairment and postpartum recovery are coupled with disruption and restoration of hippocampal circadian rhythms. Cognitive function was assessed in pregnant and postpartum women using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). In mice, four reproductive stages were compared: control, gestation, 1 month postpartum, and 3 months postpartum. Serum gonadotropins and sex hormones levels were quantified using ELISA. Home-cage locomotor activity was recorded over 48 h under a 12 h:12 h light-dark cycle. Hippocampal-dependent memory was evaluated using the novel object recognition test and Barnes maze at Zeitgeber times ZT6 (day) and ZT18 (night). Hippocampal amyloid β (Aβ) deposition was visualized via immunofluorescence; protein expression of amyloid precursor protein (APP), β-site amyloid precursor protein cleaving enzyme-1 (BACE1), and phosphorylated tau was measured by Western blots. Hippocampal clock gene expression was quantified by RT-qPCR at six time points; circadian parameters (mesor, amplitude, acrophase) were derived by cosinor analysis and compared between groups. Human cognitive screening confirmed modest gestational decline with postpartum recovery. In mice, gestation disrupted daily locomotor activity rhythms and reduced nocturnal preference; both partially recovered by 1 month and fully by 3 months postpartum. Behaviourally, pregnancy impaired the normal day-night difference and performance in novel object exploration and Barnes maze, which recovered progressively. At the molecular level, gestation increased hippocampal APP and BACE1 expression, elevated Aβ42 deposition, and induced tau hyperphosphorylation at multiple sites-hallmarks of Alzheimer's disease-related pathology. These alterations partially reversed by 1 month postpartum and normalized by 3 months. Hippocampal clock genes maintained 24 h rhythmicity, but gestation induced gene-specific phase shifts, amplitude reductions, and mesor alterations. These parameters showed gradual, gene-dependent normalization postpartum. Gestational cognitive impairment and postpartum recovery are associated with reversible disruption and restoration of both hippocampal circadian rhythms and Alzheimer's disease-related molecular pathology. These findings are correlational in nature and provide a foundation for future causal investigations.

BACKGROUND:Postoperative cognitive dysfunction (POCD) is a common disorder following surgery. The mechanisms underlying this are still under exploration. We hypothesize that hormonal changes in patients who have undergone pituitary surgery contribute to the pathogenesis of POCD. METHODS:In a 12-month follow-up study, a total of 103 patients with pituitary adenoma who received pituitary surgery were included. Patients were categorized into three groups based on their postoperative hormonal supplement: stable, sufficient, and insufficient to eliminate the effects of surgery and hormone dosage. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were employed as evaluation tools to assess the degree of cognitive impairment. RESULTS:The MoCA score in the stable group showed no significant decrease, while in the sufficient and insufficient groups, the score began to decrease from the 6th month compared to the 0 month of each group. Compared to the stable group at the same time point, the MoCA scores in both groups decreased at the 6th month and 12th month. A similar trend was observed in the MMSE score. Cognitive impairment (mild cognitive impairment and dementia) in both the sufficient group and the insufficient group increased significantly by the 3rd month after surgery, but the rate of increase was much slower subsequently in the sufficient group than in the insufficient group. CONCLUSION:Our study confirms that POCD is highly prevalent in patients after pituitary tumor surgery. Postoperative hormone deficiency plays a crucial role in the progression of POCD, especially adrenocorticotropic hormone and the glucocorticoids it affects. It is worth mentioning that a novel aspect of our study is the identification of hormonal rhythm disturbance as a potential contributor to POCD, which provides valuable insights into the mechanisms of POCD in pituitary surgery. We call for more personalized and chronobiological hormone replacement therapy approaches.

BACKGROUND:The efficacy of individual cognitive behavioral therapy (CBT) components for managing pediatric obesity remains unclear. This study systematically evaluated the impacts of CBT and its constituent techniques in this population. METHOD:We searched PubMed, Embase, and Cochrane CENTRAL from inception to July 17, 2024, for randomized controlled trials comparing CBT techniques or usual care targeting obesity management in children and adolescents with overweight or obesity. Component network meta-analyses provided estimates of effects of each component on obesity-related outcomes. We rated the certainty of evidence using modified GRADE approaches. RESULTS:We included 125 trials with 16,513 children and adolescents. For conceptual level components, compared with minimal education, behavioral therapy probably reduces body fat percentage (MD, -1.16%; 95% CI, -1.68% to -0.64%), waist circumference (MD, -1.70 cm; 95% CI, -2.74 to -0.67 cm), and improves quality of life (SMD, 0.16; 95% CI, 0.03-0.30). For technical-level components, when compared with minimal education, parental involvement (MD, -0.09; 95% CI, -0.16 to -0.03) and stimulus control (MD, -0.07; 95% CI, -0.12 to -0.01) probably reduce body mass index (BMI) z-score. Preplanning (MD, -3.05%; 95% CI, -5.82% to -0.28%) and feedback (MD, -2.73%; 95% CI, -5.31% to -0.14%) probably reduce body fat percentage, whereas device monitoring, problem-solving, rule-setting, and relaxation training might increase body fat percentage. INTERPRETATION:Behavioral therapy alone is likely effective for pediatric obesity management, irrespective of cognitive therapy integration. Techniques such as parental involvement, stimulus control, preplanning, and feedback should be prioritized in CBT.

BACKGROUND:Diabetes is associated with increased cognitive decline and dementia due to the loss of myelinated nerve fiber function, which is linked to oligodendrocyte dysfunction. The voltage-gated proton channel 1 (Hv1) is important for the cellular proton extrusion machinery. However, its role in regulating diabetes-induced cognitive dysfunction is unclear. AIM:To investigate the role of Hv1 in cognitive impairment induced by diabetes and its potential mechanisms, focusing on neuroinflammation, oligodendrocyte apoptosis, and axonal demyelination. METHODS:A diabetes model was established by administering a high-fat diet and streptozotocin injections in mice. Hv1 knockout (KO) and wild-type mice were used to evaluate cognitive function via behavioral tests and neuroinflammation using immunofluorescence. Oligodendrocyte apoptosis was assessed with the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay, and axonal demyelination was analyzed using electron microscopy. RESULTS:Hv1 expression was significantly increased in the corpus callosum of diabetic mice. Hv1 KO alleviated cognitive impairment, reduced oligodendrocyte apoptosis, and decreased the expression of inflammatory factors, including interleukin-1 and tumor necrosis factor-α, in diabetic mice. Electron microscopy revealed a reduction in myelin thickness and an increased g-ratio in diabetic mice, which were reversed by Hv1 KO. CONCLUSION:Hv1 plays a role in diabetes-induced cognitive dysfunction by modulating neuroinflammation and myelin integrity. Hv1 KO demonstrates therapeutic potential in mitigating diabetes-related cognitive decline and associated complications.

Among different age groups, middle-aged individuals are particularly susceptible to obesity, with a 22% higher risk of all-cause mortality. However, the underlying mechanisms remain unclear. In this study, we identify adipose progenitor cells (APCs) in the white adipose tissue (WAT) of middle-aged subjects as potential causes of midlife obesity. Specifically, the extracellular vesicles (EVs) derived from APCs display an impaired ability to mitigate the inflammaging of adipose tissue macrophages (ATMs) in middle-aged individuals. Mechanistically, these EVs, lacking miR-145-5p, fail to suppress the expression of L-selectin in ATMs, thereby facilitating their M1 program via the NF-κB signaling pathway. In contrast, EVs from young APCs effectively inhibit M1 macrophage polarization. Accordingly, targeted liposomes are designed to deliver miR-145-5p mimics to ATMs, which effectively prevent the obesity in middle-aged mice. Collectively, our findings highlight the role of APC-derived EVs in midlife obesity and propose miR-145-5pas a promising therapeutic target for clinical applications. Middle-aged individuals are more susceptible to obesity, but the mechanisms are unclear. Here, the authors show that extracellular vesicles from adipose progenitor cells in middle-aged individuals lack miR-145-5p, driving inflammation, and that restoring miR-145-5p could prevent midlife obesity.

Diabetes is a chronic disease that affects many people, with both its incidence and prevalence rising globally. Diabetes can lead to various complications, among which cognitive impairment in diabetic patients significantly impacts their daily life and blood glucose management, complicating treatment and worsening prognosis. Therefore, the early diagnosis and treatment of cognitive impairment are essential to ensure the health of diabetic patients. However, there is currently no widely accepted and effective method for the early diagnosis of diabetes-related cognitive impairment. This review aims to summarize potential screening and diagnostic methods, as well as biomarkers, for cognitive impairment in diabetes, including retinal structure and function examination, brain imaging, and peripheral blood biomarkers, providing valuable information and support for clinical decision making and future research.

Purpose: Diabetes has been associated with an excess risk of cognitive impairment. The hyperphosphorylation of tau protein leads to neurodegeneration and is closely related to Type 2 diabetes (T2D). This study aimed to characterize the association between P-tau181 and diabetic cognitive impairment and to develop a nomogram-based score to screen cognitive impairment in T2D patients. Methods: We used a cohort of 379 patients diagnosed with T2D as a training dataset to develop a predictive model. Risk factors associated with cognitive impairment were identified using stepwise multivariate logistic regressive analysis. A nomogram was established by incorporating these risk factors, and the diabetic cognitive impairment score (DCIS) was built and externally validated in another cohort. Results: In the training cohort, patients with cognitive impairment had higher levels of P-tau181 (13.3 [10.5-18.7] vs. 10.0 [8.0-13.0], p < 0.001). P-tau181 was negatively correlated with MOCA (r = -0.308, p < 0.001) and MMSE (r = -0.289, p < 0.001), and it was independently associated with cognitive impairment in T2D patients (OR, 1.137 [95% CI, 1.080-1.198]; p < 0.001). Other independent risk factors of diabetic cognitive impairment included age, education level, and diabetic retinopathy. The DCIS was built by nomogram based on the four risk factors, which had an area under the receiver operating characteristic curve (AUC) of 0.795 (95% CI, 0.751-0.840). The optimal cut-off of DCIS for the diagnosis of cognitive impairment in T2D patients was 139.5, with a sensitivity of 72.9% and a specificity of 75.3%. In the validation cohort, the AUC of DCIS for screening diabetic cognitive impairment was 0.770 (95% CI, 0.716-0.824). Conclusions: P-tau181 was independently associated with diabetic cognitive impairment. The DCIS, based on P-tau181, age, education level, and diabetic retinopathy, is effective to identify cognitive impairment in T2D patients.

In recent years, the prevalence of metabolic diseases has increased significantly, posing a serious threat to global health. Chronic low-grade inflammation is implicated in the development of most metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease, serving as a link between diet and these conditions. Increasing attention has been directly toward dietary inflammatory patterns that may prevent or ameliorate metabolic diseases. The Dietary Inflammatory Index (DII) was developed to assess the inflammatory potential of dietary intake. Consequently, a growing body of research has examined the associations between the DII and the risk of several metabolic diseases. In this review, we explore the current scientific literature on the relationships between the DII, T2DM, obesity, and dyslipidemia. It summarizes recent findings and explore potential underlying mechanisms from two aspects: the interaction between diet and inflammation, and the link between inflammation and metabolic diseases. Furthermore, this review discusses the therapeutic strategies, including dietary modifications, prebiotics, and probiotics, and discusses the application of the DII in metabolic diseases, as well as future research directions.

BACKGROUND:Cushing's syndrome (CS) is associated with increased risk for heart failure, which often initially manifests as left ventricular diastolic dysfunction (LVDD). In this study, we aimed to explore the potential risk factors of LVDD in CS by incorporating body composition parameters. METHODS:A retrospective study was conducted on patients diagnosed with endogenous CS no less than 18 years old. The control group consisted of healthy individuals who were matched to CS patients in terms of gender, age, and BMI. LIFEx software (version 7.3) was applied to measure epicardial adipose tissue volume (EATV) on non-contrast chest CT, as well as abdominal adipose tissue and skeletal muscle mass at the first lumbar vertebral level. Echocardiography was used to evaluate left ventricular (LV) diastolic function. Body compositions and clinical data were examined in relation to early LVDD. RESULTS:A total of 86 CS patients and 86 healthy controls were enrolled. EATV was significantly higher in CS patients compared to control subjects (150.33 cm3 [125.67, 189.41] vs 90.55 cm3 [66.80, 119.84], p < 0.001). CS patients had noticeably increased visceral fat but decreased skeletal muscle in comparison to their healthy counterparts. Higher prevalence of LVDD was found in CS patients based on LV diastolic function evaluated by E/A ratio (p < 0.001). EATV was proved to be an independent risk factor for LVDD in CS patients (OR = 1.015, 95%CI 1.003-1.026, p = 0.011). If the cut-point of EATV was set as 139.252 cm3 in CS patients, the diagnostic sensitivity and specificity of LVDD were 84.00% and 55.60%, respectively. CONCLUSION:CS was associated with marked accumulation of EAT and visceral fat, reduced skeletal muscle mass, and increased prevalence of LVDD. EATV was an independent risk factor for LVDD, suggesting the potential role of EAT in the development of LVDD in CS.

BACKGROUND:Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. METHODS:The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB-/- mice were generated, and relevant in vivo experiments were performed. RESULTS:Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB-/- mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. CONCLUSION:Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Type 2 diabetes mellitus (T2DM), accounting for the majority of diabetes mellitus prevalence, is associated with an increased risk of cognition decline and deterioration of cognition function in diabetic patients. The sodium–glucose cotransporter 2 (SGLT2), located in the renal proximal tubule, plays a role in urine glucose reabsorption. SGLT2 inhibitors (SGLT2i), have shown potential benefits beyond cardiac and renal improvement in preventing and treating cognitive impairment (CI), including mild cognitive impairment, Alzheimer’s disease and vascular dementia in T2DM patients. Studies suggest that SGLT2i may ameliorate diabetic CI through metabolism pathways, inflammation, oxidative stress, neurotrophic factors and AChE inhibition. Clinical trials and meta-analyses have reported significant and insignificant results. Given their vascular effects, SGLT2i may offer unique protection against vascular CI. This review compiles mechanisms and clinical evidence, emphasizing the need for future analysis, evaluation, trials and meta-analyses to verify and recommend optimal SGLT2i selection and dosage for specific patients.

Previous studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk. This retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes. A total of 1,488 (20.3

AIMS/INTRODUCTION:To assess whether the sodium-glucose cotransporter 2 inhibitor, henagliflozin, improves cognitive impairment in patients with type 2 diabetes. MATERIALS AND METHODS:We carried out a prospective study on 290 patients with type 2 diabetes and cognitive impairment. Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels were used to assess cognition. The association between henagliflozin use and changes in cognition was examined using multivariable logistic regression analysis. RESULTS:Montreal Cognitive Assessment scores at enrollment and after 6 months were 21 (interquartile range [IQR]19-23) versus 22 (IQR 20-25; P < 0.0001) in all patients, 21 (IQR 19-23) versus 24 (IQR 22-26; P < 0.0001) in the henagliflozin group and 21 (IQR 19-22) versus 21 (IQR 19-23; P > 0.05) in the non-sodium-glucose cotransporter 2 inhibitor group. Logistic regression analysis showed that henagliflozin treatment was associated with Montreal Cognitive Assessment score improvement independent of potential confounders (odds ratio [OR] 3.670, 95% confidence interval [CI] 2.224-6.056, P < 0.0001). Additionally, plasma phosphorylated tau181 levels significantly decreased at 6-month follow up in all patients (OR 11.5, 95% CI 9.9-13.7 vs OR 10.1, 95% CI 7.8-12.9, P < 0.0001) and in the henagliflozin group (OR 11.5, 95% CI 10.3-13.0 vs OR 9.2, 95% CI 7.1-10.7, P < 0.0001), but not in the non-sodium-glucose cotransporter 2 inhibitor group. Henagliflozin treatment was independently associated with decreased phosphorylated tau181 levels (OR 3.670, 95% CI 1.598-4.213, P < 0.0001). CONCLUSIONS:Henagliflozin treatment was independently associated with improvements in Montreal Cognitive Assessment scores and plasma phosphorylated tau181 levels, indicating significant beneficial effects on cognitive impairment in patients with type 2 diabetes.

Background: Cognitive impairment is a prevalent complication of type 2 diabetes, influenced significantly by various dietary patterns. High-carbohydrate diets (HCDs) are commonly consumed nowadays; however, the specific impact of HCDs on cognitive function in diabetes remains unclear. Methods: The objective of this study was to investigate whether an HCD has effects on cognition in diabetes. Eight-week-old diabetic (db/db) mice and wild-type (WT) mice underwent a twelve-week dietary intervention, including a normal diet (ND), an HCD, or a high-fat diet (HFD). Following this, behavioral tests were conducted, and related hippocampal pathology was evaluated. Results: Our results demonstrated that an HCD exacerbated cognitive decline in db/db mice compared to an ND. Additionally, an HCD increased amyloid-β burden and expression of β-site APP cleaving enzyme-1. An HCD was also found to promote the phosphorylation of tau protein via the PI3K/Akt/GSK-3β pathway. Furthermore, an HCD markedly induced neuroinflammation and increased the quantity of microglia and astrocytes. However, these damages induced by an HCD were less severe than those caused by an HFD. Conclusions: Collectively, our findings indicate that a high intake of carbohydrates can have an adverse impact on cognitive function in diabetes.

Background: An antidiabetic medication regimen is crucial for maintaining glycemic control. Type 2 diabetes mellitus (T2DM) and cognitive dysfunction have a bidirectional relationship. This study aims to explore the impact that adjusting antidiabetic medication regimens has on medication adherence, glycemic control, and cognitive function in patients with T2DM and mild cognitive impairment (MCI). Methods: This is an observational cross-sectional analysis that includes 364 consecutive inpatients with T2DM. Clinical data were collected, medication adherence was assessed using the Medication Adherence Report Scale (MARS-5), and cognitive status was evaluated using the Chinese version of the Montreal Cognitive Assessment (MoCA) and Mini-mental State Examination (MMSE). These data were obtained both during hospitalization and at a three-month follow-up. Multivariable logistic regression analysis was applied to determine the association between changes in medication regimens and medication adherence, glycemic control, and cognitive function. Results: Baseline medication adherence was high across all three different cognitive status groups, with no significant difference in MARS-5 scores. At the 3-month follow-up, the group with a high adjustment ratio of antidiabetic medication regimens showed an increase in their hemoglobin A1c (HbA1c) level compared to the baseline, while the group with a low adjustment ratio showed a decrease in this level. In addition, the MoCA, MMSE, and MARS-5 scores of the high-adjustment group were significantly lower than those of the low-adjustment group. Conclusions: A high ratio of medication adjustment was significantly associated with worse medication adherence and glycemic control in T2DM patients with MCI. Patients with a low ratio of medication adjustment had good adherence and better glycemic control. Clinicians should take cognitive status into account when adjusting antidiabetic regimens for T2DM patients and may need to provide additional guidance to patients with cognitive impairment to improve adherence and glycemic outcomes.

Abstract Aims This study aims to analyze the association between combustible/electronic cigarettes and the risk of stroke. Methods We obtained data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). The stroke history and combustible/electronic cigarette use were acquired by questionnaires. Considering the sole or dual use of combustible cigarettes and electronic cigarettes (e-cigarettes), we divided all the individuals into four subgroups, including nonsmokers (reference group), sole combustible cigarette, sole e-cigarette, and dual use of both combustible cigarettes and e-cigarettes. We performed multivariable logistic regression to determine the association between cigarette use with the prevalence of stroke. We used odds ratios (ORs) with 95% confidence intervals (CIs) to show the effect size. Finally, we developed a prediction model to evaluate the risk of stroke for individuals with combustible or electronic cigarette use based on a random forest model. Results We included a total of 4022 participants in the study. The median age was 55, and 48.3% of the participants were males. When we adjusted for age, gender, education attainment, race, total-to-HDL cholesterol (< 5.9 or ≥ 5.9), diabetes, hypertension, and alcohol consumption, the groups of sole e-cigarette use, sole combustible cigarette use, and dual use of combustible and electronic cigarettes were significantly associated with the prevalence of stroke with ORs (with 95%CI) of 2.07 (1.04–3.81), 2.36 (1.52–3.59), 2.34 (1.44–3.68), respectively. In the testing set, the AUC was 0.74 (95%CI = 0.65–0.84), sensitivity was 0.68, and specificity was 0.75. Conclusion Sole e-cigarettes and dual use of e-cigarettes with combustible cigarettes might increase the risk of stroke.

Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB −/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH.